Current strategies to target the anti-apoptotic Bcl-2 protein in cancer cells.

Apoptosis (or programmed cell death) is a genetically controlled "cell suicide" pathway which plays an essential role in deleting excess, unwanted or damaged cells during development and tissue homeostasis. Dysregulation of apoptosis contributes to a wide variety of pathological conditions, including AIDS, cardiovascular disease, infectious disease, autoimmunity and neurodegenerative disorders. Resistance to apoptosis is also a common feature in human malignancies, contributing to both the development of cancer and resistance to conventional therapies such as radiation and cytotoxic drugs, which function by activating apoptotic cell death pathways. Bcl-2 is one of the best characterized cell death control proteins; its overexpression confers resistance to a broad range of apoptosis inducers and the cell survival functions of Bcl-2 are activated by translocation in lymphomas and overexpression in many other cancer types. A wealth of experimental data supports the idea that Bcl-2 is an attractive and tractable target for newer molecularly directed anti-cancer strategies, designed to promote cancer cell death. Here we review current understanding of the mechanism of action and importance of Bcl-2 in cancer cells and progress in developing new agents to target this key survival molecule.